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H5N1 is a strain of flu that originally was found in birds, but can infect livestock, and humans. This study made small changes in a lab to a strain that occurs in cows and found that a single mutation makes the virus much more specific to humans. Potentially, it could make it much easier for the virus to infect humans.
It’s worth noting that these mutations have not been observed in the wild, the study aims to show how small changes could have large implications.
Prof Kingston Mills, Professor of Experimental Immunology and Director of Trinity Biomedical Sciences Institute, Trinity College Dublin, said:
“A highly pathogenic avian influenza virus (H5N1 clade 2.3.4.4b) was detected in cattle in Texas in March 2024 and has since spread to over 600 cattle herds and poultry flocks in 15 US states. There have been 50 cases of human infection with the H5N1 virus in the US and one in Canada, mostly in farm workers.
Sequencing studies on virus from infected individuals have shown amino acid substitutions have occurred in crucial haemagglutinin component of the H5N1 virus, which suggest adaption to humans. However, there is no clear evidence yet of human-to-human transmission.
The study from the Ian Wilson’s research group in La Jolla, California has shown that a single amino acid substitution in the receptor binding region of influenza virus haemagglutinin protein from the virus that had transmitted from cattle to humans would facilitate binding of the virus to human cells. This mutation has not yet been detected in the H5N1 virus in humans, but if it did occur it suggests that human-to-human transmission would be facilitated, resulting in a significant risk of a future influenza pandemic.
Current seasonal influenza virus vaccines protect against seasonal influenza viruses but will not protect against the highly pathogenic avian H5N1 influenza virus. Although the H5N1 vaccines from the 2009 avian pandemic may provide some protection, they will need to be update to be fully effective against the current H5N1 avian clade 2.3.4.4b influenza virus.”
Dr Gerald Barry, Lecturer/Assistant Professor, School of Veterinary Medicine, University College Dublin (UCD), said:
“Influenza virus has the ability to infect humans as well as multiple types of animals including birds, horses, dogs, cats, pigs, foxes, badgers and cattle. Different versions of influenza tend to infect the same species all the time, but occasionally a version can move between species including from animals to humans. There is an ongoing outbreak of an avian (bird) version of influenza that is spreading among different wildlife globally, and it has led to huge numbers of animal deaths over recent years as well as increased numbers of sick animals globally. In recent months, cases of this avian version have appeared in cattle in North America. This has also led to a small number of farm workers getting infected. A bird is very different from a mammal. If a virus like influenza is adapted to a bird, then for it to jump to a mammal takes a relatively large evolutionary leap, however, once it has adapted, even a little bit, to a mammalian system, as is the case in cattle now, then the gap to adapting to humans and learning how to spread and cause disease in humans is potentially not as big.
This means that the risk to humans becomes greater. In that context, a recent publication has shown that some versions of the virus that have infected cattle farm workers have a small change in their makeup that makes them a bit more adapted to humans, potentially increasing its ability to spread and cause disease in humans. This is important because it means that small changes can make a big difference and that this virus is something we need to keep a very close eye on, as it moves closer and closer to being able to cause major outbreaks of disease in humans. Increased surveillance and a true One Health approach to managing influenza globally is needed.
The major strength of this publication is that it is looking at real cases from humans and animals, rather than working on hypotheticals or ‘what ifs’. It is limited because the adaptations it is talking about are based on laboratory experiments rather than real world experiences, so although this increased adaptation to humans has appeared, based on lab experiments, it doesn’t necessarily guarantee that the changes seen will in fact lead to greater spread in humans.”
Prof Stuart Elborn, Professor of Medicine and Deputy Vice Chancellor, Queen’s University Belfast (QUB), said:
“This is a well conducted study and I think highlights the importance of surveillance particularly for known viruses that do jump species. The main finding is as below
“Analysis of the hemagglutinin (HA) from the first-reported human-infecting bovine H5N1 virus (A/Texas/37/2024, Texas) revealed avian-type receptor binding preference.”
“A switch from avian- to human-type recep[1]tor specificity is considered a major risk factor for transmission in humans (33, 35, 64). For this reason, our observation that the single Texas H5 HA Gln226Leu mutation can switch receptor specificity is a clear concern.”
These switches do occur in avian flu and it is both interesting and important to recognise that this may also occur in bovine species and may indeed occur in other species and with other viruses.
Viruses are highly prone to mutations and this is a very well conducted study looking at the science of this but is not unexpected that one or two mutations result in the virus having a human specificity.
My views this further highlights the importance of ongoing surveillance particularly of known viruses such as influenza which can jump species. It further emphasises the importance of a “one health” approach to infectious diseases.”
‘A single mutation in bovine influenza H5N1 hemagglutinin switches specificity to human receptors’ by Lin et. al was published in Science at 19:00 Irish time Thursday 5th December 2024.
DOI: https://doi.org/10.1126/science.adt0180